Alveolar macrophages play a paramount role in maintaining lung homeostasis. Environmental agents, implicated in the etiology of chronic obstructive lung disease have been shown to alter macrophage behavior; and it is hypothesized that these alterations are critical to the development of the disease. We suggest that the pinocytic activity of alveolar macrophages is responsible for removal from the alveoli of hydrolytic enzymes and other agents which promote tissue damage. To evaluate this hypothesis we propose a comprehensive study of the factors that regulate, as well as, the mechanism of pinocytosis in rabbit alveolar macrophages in vitro. Using quantitative assays to measure pinocytosis, we will evaluate the effect of environmental pollutants, as well as other agents, on pinocytic rate in alveolar macrophages in vitro. To directly determine the ability of macrophages to sequester hydrolytic enzymes, leukocytic lysosomal enzymes will be isolated and the ability of macrophages to sequester these enzymes determined. Additionally, we also propose to define the interaction between alpha2-macroglobulin-protease complexes and macrophage surface receptors. We also propose to examine if alterations in pinocytic activity alters the concentration of membrane proteins. We also plan to isolate and characterize pinocytic vesicles. The ability to isolate pinocytic vesicles will allow us to critically examine the "recycling" hypothesis, which states that plasma membrane proteins internalized during pinocytic activity return to plasma membranes in an undegraded form. These studies will lead to a better understanding of the physiology of alveolar macrophages and of the effect of environmental agents on this cell type.